4-Hydroxy-7-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester | 914782-11-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-Hydroxy-7-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester
• 英文别名: methyl 4-hydroxy-7-methyl-1,1-dioxo-2H-1lambda6,2-benzothiazine-3-carboxylate；methyl 4-hydroxy-7-methyl-1,1-dioxo-2H-1λ6,2-benzothiazine-3-carboxylate
• CAS: 914782-11-9
• 化学式: C₁₁H₁₁NO₅S
• 分子量: 269.278
• InChiKey: WKJXJVZAWFHMFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-7-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 xylene 为溶剂， 反应 72.0h， 生成 4-Hydroxy-2,7-dimethyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide
  参考文献：
  名称：

  Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

  摘要：

  Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

  DOI：

  10.1021/jm9607010
• 作为产物：
  描述：

  6-甲基-1,1-二氧代-1,2-苯并噻唑-3-酮 在 甲醇 、 sodium methylate 、 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 8.5h， 生成 4-Hydroxy-7-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

  摘要：

  Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

  DOI：

  10.1021/jm9607010

文献信息

• Synthesis of Potential Biologically Active 1,2-Benzothiazin-3-yl-quinazolin-4(3H)-ones
  作者：Muhammad Zia-ur-Rehman、Jamil Anwar Choudary、Saeed Ahmad、Hamid Latif Siddiqui

  DOI：10.1248/cpb.54.1175

  日期：——

  A series of potential biologically active 2-(4-hydroxy-1,1-dioxido-2H-1,2-benzothiazin-3-yl)quinazolin-4(3H)-ones was synthesized in a straight forward manner by condensation of respective 4-hydroxy-1,2-benzothiazine-1,1-dioxides with anthranilamide followed by simple and high throughput cyclization of N-[2-(aminocarbonyl)phenyl]-4-hydroxy-1,2-benzothiazine-3-carboxamide-1,1-dioxides. All the synthesized compounds were subjected to preliminary evaluation for their biological activity against Gram positive and Gram negative bacteria. Some of the assayed compounds showed marked activity against Bacillus subtilis.

  2-苯并噻嗪-3-基）喹唑啉-4(3H)-酮的简单高通量环化反应。对所有合成化合物进行了初步评估，以确定其对革兰氏阳性和革兰氏阴性细菌的生物活性。其中一些化合物对枯草杆菌具有明显的活性。
• US4233299A
  申请人：——

  公开号：US4233299A

  公开（公告）日：1980-11-11